This Core will facilitate the testing of lead compounds arising from our various enzyme screens in Projects 1-4, firstly, in an established macrophage infection mouse mode and, secondly, in an established aerosol mouse infection model, by our colleague Dr. Ian Orme and staff, under the support of NIH, NIAID, NCDDG-OI Contract AI-45239, "Animal Model Testing of TB Drugs." The minimal inhibitory concentration (MIC) of promising leads arising from Projects 1-4 will be tested by Dr. Phetsuksiris, supported through Project 1, using a modified microdrop agar proportion test, and by broth culture, and, in the case of drug-resistant strains, by a microplate-colony protocol. Under this Core, we also plan to conduct limited cytotoxicity testing of promising products by a microplate alamar blue assay before submitting for more comprehensive testing to the NIH-sponsored TAACF (Tuberculosis Antimicrobial Acquisition and Coordinating Facility).